Nasal delivery devices

ABSTRACT

A nasal delivery device comprising: a housing ( 15 ); a nosepiece ( 17 ) for fitting to a nasal cavity of a subject; a mouthpiece ( 19 ) through which the subject in use exhales; and a substance supply unit ( 21 ) including an actuation member ( 23 ) which extends from one end of the housing and is manually actuated to deliver substance to the nasal cavity of the subject; wherein the housing includes a grip section ( 27 ) which is disposed at the one end of the housing from which the actuation member extends, said grip section comprising a first, distal part ( 28 ) including at least one projecting grip element ( 29 ) by which the subject grips the housing in actuating the actuation member, and a second, proximal part ( 31 ) providing a recess ( 33 ) in which fingers of the subject are located, said recess promoting proper orientation of the delivery device in a hand of the subject.

The present invention relates to a nasal delivery device for and amethod of delivering substances, in particular one of a liquid, as asuspension or solution, or a powder, containing a medicament, especiallysystemic or topical pharmaceuticals, or a vaccine, to the nasal airwayof a subject.

Referring to FIG. 5, the nasal airway 1 comprises the two nasal cavitiesseparated by the nasal septum, which airway 1 includes numerous ostia,such as the paranasal sinus ostia 3 and the tubal ostia 5, and olfactorycells, and is lined by the nasal mucosa. The nasal airway 1 cancommunicate with the nasopharynx 7, the oral cavity 9 and the lowerairway 11, with the nasal airway 1 being in selective communication withthe anterior region of the nasopharynx 7 and the oral cavity 9 byopening and closing of the oropharyngeal velum 13. The velum 13, whichis often referred to as the soft palate, is illustrated in solid line inthe closed position, as achieved by providing a certain positivepressure in the oral cavity 9, such as achieved on exhalation throughthe oral cavity 9, and in dashed line in the open position.

There are many nasal conditions which require treatment. One suchcondition is nasal inflammation, specifically rhinitis, which can beallergic or non-allergic and is often associated with infection andprevents normal nasal function. By way of example, allergic andnon-allergic inflammation of the nasal airway can typically effectbetween 10 and 20% of the population, with nasal congestion of theerectile tissues of the nasal concha, lacrimation, secretion of waterymucus, sneezing and itching being the most common symptoms. As will beunderstood, nasal congestion impedes nasal breathing and promotes oralbreathing, leading to snoring and sleep disturbance. Other nasalconditions include nasal polyps which arise from the paranasal sinuses,hypertrophic adenoids, secretory otitis media, sinus disease and reducedolfaction.

In the treatment of certain nasal conditions, the topical administrationof medicaments is preferable, particularly where the nasal mucosa is theprime pathological pathway, such as in treating or relieving nasalcongestion. Medicaments that are commonly topically delivered includedecongestants, anti-histamines, cromoglycates, steroids and antibiotics.At present, among the known anti-inflammatory pharmaceuticals, topicalsteroids have been shown to have an effect on nasal congestion. Topicaldecongestants have also been suggested for use in relieving nasalcongestion. The treatment of hypertrophic adenoids and chronic secretoryotitis media using topical decongestants, steroids and anti-microbialagents, although somewhat controversial, has also been proposed.Further, the topical administration of pharmaceuticals has been used totreat or at least relieve symptoms of inflammation in the anteriorregion of the nasopharynx, the paranasal sinuses and the auditory tubes.

Medicaments can also be systemically delivered through the nasalpathway, the nasal pathway offering a good administration route for thesystemic delivery of pharmaceuticals, such as hormones, for example,oxytocin and calcitonin, and analgetics, such as anti-migrainecompositions, as the high blood flow and large surface area of the nasalmucosa advantageously provides for rapid systemic uptake.

Nasal delivery is also expected to be advantageous for theadministration of medicaments requiring a rapid onset of action, forexample, analgetics, anti-emetics, insulin, anti-epileptics, sedativesand hypnotica, and also other pharmaceuticals, for example,cardio-vascular drugs. It is envisaged that nasal administration willprovide for a fast onset of action, at a rate similar to that ofinjection and at a rate much faster than that of oral administration.Indeed, for the treatment of many acute conditions, nasal administrationis advantageous over oral administration, since gastric stasis canfurther slow the onset of action following oral administration.

It is also expected that nasal delivery could provide an effectivedelivery route for the administration of proteins and peptides asproduced by modern biotechnological techniques. For such substances, themetabolism in the intestines and the first-pass-effect in the liverrepresent significant obstacles for reliable and cost-efficientdelivery.

Furthermore, it is expected that nasal delivery using the nasal deliverytechnique of the present invention will prove effective in the treatmentof many common neurological diseases, such as Alzheimer's, Parkinson's,psychiatric diseases and intracerebral infections, where not possibleusing existing techniques. The nasal delivery technique of the presentinvention allows for delivery to the olfactory region, which region islocated in the superior region of the nasal cavities and represents theonly region where it is possible to circumvent the blood-to-brainbarrier (BBB) and enable communication with the cerebrospinal fluid(CSF) and the brain.

Also, it is expected that the nasal delivery technique of the presentinvention will allow for the effective delivery of vaccines.

Aside from the delivery of medicaments, the irrigation of the nasalmucosa with liquids, in particular saline solutions, is commonlypractised to remove particles and secretions, as well as to improve themucociliary activity of the nasal mucosa. These solutions can be used incombination with active pharmaceuticals.

For any kind of drug delivery, accurate and reliable dosing isessential, but it is of particular importance in relation to theadministration of potent drugs which have a narrow therapeutic window,drugs with potentially serious adverse effects and drugs for thetreatment of serious and life-threatening conditions. For someconditions, it is essential to individualize the dosage to theparticular situation, for example, in the case of diabetes mellitus. Fordiabetes, and, indeed, for many other conditions, the dosage of thepharmaceutical is preferably based on actual real-time measurements.

Currently, blood samples are most frequently used, but the analysis ofmolecules in the exhalation breath of subjects has been proposed as analternative to blood analysis for several conditions. Breath analysis iscurrently used for the diagnosis of conditions such as helicobacterpylori infections which cause gastric ulcers.

WO-A-2000/051672 discloses a delivery device for delivering a substance,in particular a medicament, in a bi-directional flow through the nasalcavities, that is, an air flow which passes into one nostril, around theposterior margin of the nasal septum and in the opposite direction outof the other nostril. This bi-directional air flow advantageously actsto stimulate the sensory nerves in the nasal mucosa, therebyconditioning the subject for the delivery and providing a morecomfortable delivery situation.

It is an aim of the present invention to provide nasal delivery devicesand methods for delivering substances to a nasal cavity of subject, andin particular relatively-simple mechanically-actuatable deliverydevices.

In one aspect the present invention provides a nasal delivery device fordelivering substance to a nasal cavity of a subject, the delivery devicecomprising: a housing; a nosepiece for fitting to a nasal cavity of asubject; a mouthpiece through which the subject in use exhales; and asubstance supply unit, which includes an actuation member which extendsfrom one end of the housing and is manually actuated to deliversubstance to the nasal cavity of the subject; wherein the housingincludes a main body section, from one, base end of which extends theactuation member of the substance supply unit, and a grip section, whichis disposed at the one end of the main body section, the grip sectioncomprising a first, distal part which includes at least one projectinggrip element by which the subject grips the housing in actuating theactuation member of the substance supply unit, and a second, proximalpart which provides a recess in which fingers of the subject arelocated, whereby the recess promotes proper orientation of the deliverydevice in a hand of the subject.

In one embodiment the main body section comprises an elongate section.

In one embodiment the at least one projecting grip element is acircumferential lip which extends around or substantially around theperiphery of the housing.

In another embodiment the distal part of the grip section comprisesfirst and second projecting grip elements, which project to oppositesides of the housing, with no intermediate elements.

In one embodiment the first and second projecting grip elements arealigned on an axis common with that of the mouthpiece.

In another aspect the present invention provides a method of deliveringsubstance to a nasal cavity of a subject, the method comprising thesteps of: providing a nasal delivery device, comprising: a housing; anosepiece for fitting to a nasal cavity of the subject; a mouthpiecethrough which the subject exhales; and a substance supply unit, whichincludes an actuation member which extends from one end of the housingand is manually actuated to deliver substance to the nasal cavity of thesubject; wherein the housing includes a main body section, from one,base end of which extends the actuation member of the substance supplyunit, and a grip section, which is disposed at the one end of the mainbody section, the grip section comprising a first, distal part whichincludes at least one projecting grip element by which the subject gripsthe housing in actuating the actuation member of the substance supplyunit, and a second, proximal part which provides a recess in whichfingers of the subject are located; fitting the nosepiece to the nasalcavity of the subject; locating the mouthpiece in the mouth of thesubject; and gripping the housing such that fingers of the subject arelocated in the recess to opposite sides of the housing and adjacent theat least one projecting grip part, thereby promoting proper orientationof the delivery device in a hand of the subject to effect operation ofthe delivery device.

In one embodiment the main body section comprises an elongate section.

In one embodiment the at least one projecting grip element is acircumferential lip which extends around or substantially around theperiphery of the housing.

In another embodiment the distal part of the grip section comprisesfirst and second projecting grip elements, which project to oppositesides of the housing, with no intermediate elements.

In one embodiment the first and second projecting grip elements arealigned on an axis common with that of the mouthpiece.

Preferred embodiments of the present invention will now be describedhereinbelow by way of example only with reference to the accompanyingdrawings, in which:

FIG. 1 illustrates a perspective view of a nasal delivery device inaccordance with a first embodiment of the present invention;

FIGS. 2( a) and (b) illustrate orthogonal side views of the deliverydevice of FIG. 1;

FIG. 3 illustrates a perspective view of a nasal delivery device inaccordance with a second embodiment of the present invention;

FIGS. 4( a) and (b) illustrate orthogonal side views of the deliverydevice of FIG. 3; and

FIG. 5 schematically illustrates the anatomy of the upper respiratorytract of a human subject.

FIGS. 1 and 2 illustrate a nasal delivery device in accordance with afirst embodiment of the present invention.

The delivery device comprises a housing 15, a nosepiece 17 for fittingin a nasal cavity of a subject, a mouthpiece 19 through which thesubject in use exhales, and a substance supply unit 21, which includesan actuation member 23 which extends from one end of the housing 15 andis manually actuated to deliver substance to the nasal cavity of thesubject.

The housing 15 includes a main body section 25, in this embodiment anelongate section, from one, base end of which extends the actuationmember 23 of the substance supply unit 21.

The housing 15 further includes a grip section 27, which is disposed atthe one end of the main body section 25.

The grip section 27 comprises a first, distal part 28 which includes atleast one projecting grip element 29 by which a user grips the housing15, typically between fingers, in actuating the actuation member 23 ofthe substance supply unit 21, and a second, proximal part 31 whichprovides a recess or waist 33 in which the fingers of the user arelocated.

In this embodiment the projecting grip element 29 is a circumferentialflange or lip which extends around or substantially around the peripheryof the housing 15.

The present inventors have recognized that the provision of the recessor waist 33 adjacent the flange or lip element 29 promotes properorientation of the delivery device in the hand of the user, insofar as auser is required to orient the delivery device in a particular manner inthe nasal cavity, in order to achieve optimal performance from thedelivery device.

FIGS. 3 and 4 illustrate a nasal delivery device in accordance with asecond embodiment of the present invention.

The delivery device of this embodiment is very similar to theabove-described first embodiment, and thus, in order to avoidunnecessary duplication of description, only the differences will bedescribed in detail.

In this embodiment the distal part 28 of the grip section 27 comprisesfirst and second projecting grip elements 29 a, 29 b, which project toopposite sides of the housing 15, with no intermediate elements. In thisembodiment the first and second projecting grip elements 29 a, 29 b arealigned on an axis common with that of the mouthpiece 19.

The present inventors have recognized that this configuration promotes aproper rotational orientation of the delivery device when gripped in thehand of a user, insofar as a user is required to orient the deliverydevice in a particular manner in the nasal cavity, in order to achieveoptimal performance from the delivery device.

Finally, it will be understood that the present invention has beendescribed in its preferred embodiments and can be modified in manydifferent ways without departing from the scope of the invention asdefined by the appended claims.

1. A nasal delivery device for delivering substance to a nasal cavity of a subject, the delivery device comprising: a housing; a nosepiece for fitting to a nasal cavity of a subject; a mouthpiece through which the subject in use exhales; and a substance supply unit, which includes an actuation member which extends from one end of the housing and is manually actuated to deliver substance to the nasal cavity of the subject; wherein the housing includes a main body section, from one, base end of which extends the actuation member of the substance supply unit, and a grip section, which is disposed at the one end of the main body section, the grip section comprising a first, distal part which includes at least one projecting grip element by which the subject grips the housing in actuating the actuation member of the substance supply unit, and a second, proximal part which provides a recess in which fingers of the subject are located, whereby the recess promotes proper orientation of the delivery device in a hand of the subject.
 2. The delivery device of claim 1, wherein the main body section comprises an elongate section.
 3. The delivery device of claim 1, wherein the at least one projecting grip element is a circumferential lip which extends around or substantially around the periphery of the housing.
 4. The delivery device of claim 1, wherein the distal part of the grip section comprises first and second projecting grip elements, which project to opposite sides of the housing, with no intermediate elements.
 5. The delivery device of claim 4, wherein the first and second projecting grip elements are aligned on an axis common with that of the mouthpiece.
 6. A method of delivering substance to a nasal cavity of a subject, the method comprising the steps of: providing a nasal delivery device, comprising: a housing; a nosepiece for fitting to a nasal cavity of the subject; a mouthpiece through which the subject exhales; and a substance supply unit, which includes an actuation member which extends from one end of the housing and is manually actuated to deliver substance to the nasal cavity of the subject; wherein the housing includes a main body section, from one, base end of which extends the actuation member of the substance supply unit, and a grip section, which is disposed at the one end of the main body section, the grip section comprising a first, distal part which includes at least one projecting grip element by which the subject grips the housing in actuating the actuation member of the substance supply unit, and a second, proximal part which provides a recess in which fingers of the subject are located; fitting the nosepiece to the nasal cavity of the subject; locating the mouthpiece in the mouth of the subject; and gripping the housing such that fingers of the subject are located in the recess to opposite sides of the housing and adjacent the at least one projecting grip part, thereby promoting proper orientation of the delivery device in a hand of the subject to effect operation of the delivery device.
 7. The method of claim 6, wherein the main body section comprises an elongate section.
 8. The method of claim 6, wherein the at least one projecting grip element is a circumferential lip which extends around or substantially around the periphery of the housing.
 9. The method of claim 6, wherein the distal part of the grip section comprises first and second projecting grip elements, which project to opposite sides of the housing, with no intermediate elements,
 10. The delivery device of claim 9, wherein the first and second projecting grip elements are aligned on an axis common with that of the mouthpiece. 